Genetic Variant S100A4:p.Gly47Arg (chr1-153544656-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002961.3(S100A4):c.139G>A(p.Gly47Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

S100A4
NM_002961.3 missense, splice_region

Scores

Splicing: ADA: 0.002304

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

0 publications found

Variant links:

Genes affected

S100A4 (HGNC:10494): (S100 calcium binding protein A4) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

S100A4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3072049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002961.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A4	NM_002961.3	MANE Select	c.139G>A	p.Gly47Arg	missense splice_region	Exon 2 of 3	NP_002952.1	P26447
	S100A4	NM_019554.3		c.139G>A	p.Gly47Arg	missense splice_region	Exon 3 of 4	NP_062427.1	P26447

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A4	ENST00000368716.9	TSL:1 MANE Select	c.139G>A	p.Gly47Arg	missense splice_region	Exon 2 of 3	ENSP00000357705.4	P26447
S100A4	ENST00000354332.8	TSL:1	c.139G>A	p.Gly47Arg	missense splice_region	Exon 3 of 4	ENSP00000346294.4	P26447
S100A4	ENST00000481009.1	TSL:1	n.442G>A		splice_region non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.62

M_CAP

Benign

0.026

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.2

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.078

Sift

Benign

0.15

Sift4G

Benign

0.15

Polyphen

0.71

Vest4

0.17

MutPred

0.46

Gain of solvent accessibility (P = 0.0097)

MVP

0.59

MPC

0.36

ClinPred

0.95

GERP RS

3.9

PromoterAI

0.084

Neutral

(source)

Varity_R

0.41

gMVP

0.45

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0023

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over